Various Aspects of Profiling the Metabolome in Human Pathogenic Yeasts Using Gas Chromatography-Mass Spectrometry

Abstract

Human pathogenic yeasts of the genus Candida and 𝘊𝘳𝘺𝘱𝘵𝘰𝘤𝘰𝘤𝘤𝘶𝘴 𝘯𝘦𝘰𝘧𝘰𝘳𝘮𝘢𝘯𝘴 are responsible for about 10% of hospital-acquired infections. In addition, drug-resistant yeasts are rapidly emerging with the use of anti-fungal drugs. Common drugs such as Fluconazole and Amphotericin B target the ergosterol pathway in yeast. Learning about other metabolic differences in yeasts may also give a new understanding to their role as pathogens. Metabolomics is a field of study about the large spectrum of metabolites necessary for the growth and survival of an organism. Gas chromatography-mass spectrometry (GC-MS) was used to analyze the metabolome of different yeasts in three different studies. The first study was a targeted analysis of the ergosterol pathway in 𝘊𝘢𝘯𝘥𝘪𝘥𝘢 𝘢𝘭𝘣𝘪𝘤𝘢𝘯𝘴 and a double drug-resistant mutant was found to have several changes in its sterol composition while Fluconazole-resistant strains were similar to the wild-type. In the second study, a comprehensive analysis of the polar and lipid metabolite profiles of six pathogenic yeasts revealed that lipid profiles were more conserved than polar profiles, thereby better reflecting their taxonomical relationship according to 265 rRNA sequences. However, there were several potential species-specific metabolites and short regions in the metabolite profiles with enough peak differentiation that could be used to rapidly distinguish between these yeasts by visual inspection. In the third study, the metabolic phenotypes of three strains of 𝘊𝘳𝘺𝘱𝘵𝘰𝘤𝘰𝘤𝘤𝘶𝘴 𝘯𝘦𝘰𝘧𝘰𝘳𝘮𝘢𝘯𝘴 were analysed to determine the extent of contribution of the metabolite phenotypes from two parents to their hybrid offspring. While the lipid metabolite phenotypes of all strains resembled each other, the polar metabolite phenotype of the hybrid offspring strongly resembled one parent but not the other.